Lacosamide is the (R)-enantiomer of N-benzyl-2-acetamido-3-methoxypropionamide (FIG. 1) recently approved by FDA (October, 2008) as an add-on therapy for partial-onset seizures in adults with epilepsy. Epilepsy is a complex neurological disorder characterized by recurrent spontaneous seizures and it affects almost 50 million people worldwide. The life time prevalence of this disease is 1% and it affects individuals of all ages regardless of gender or socio-economic status. Further, epilepsy requires prolonged and sometimes lifelong drug therapy.
Although the mechanism of action of Lacosamide is not yet clearly understood, but it is believed that it enhances slow inactivation of voltage-gated Na+ channels and binds to dihydropyrimidinase-related protein 2 (CRMP 2), and thus controls the seizures. Due to this unique mode of action, it differs from other antiepileptic drugs (AEDs). Commercially, Lacosamide is prepared using a chiral pool approach starting from unnatural amino acid D-serine and its derivatives.

Lacosamide and its methods of preparation are disclosed in Reissue U.S. Pat. No. RE 38,551, involves reaction of protected and deprotected active groups (such as amino, hydroxyl and carboxylic group) of D-serine derivatives that subsequently yield lacosamide.
An alternative method for the preparation of Lacosamide is disclosed in PCT publication WO 2006/037574 which involves O-methylation of N-Boc-protected-D-serine (“Boc” refers to t-butoxycarbonyl) directly in one step by avoiding simultaneous formation of the methyl ester moiety. WO/2011/095995 also discloses an alternate process for preparation of lacosamide. Further, intermediate compounds such as D-serinamide derivatives and their use in the preparation of lacosamide are disclosed in US20090143472 and WO2011039781. References may be made to patent application US20110130350, wherein improved method for preparation of Lacosamide is disclosed, wherein the intermediate (R)-2-N-Boc-amino-3-methoxypropanoic acid is prepared from N-Boc-D-serine using phase transfer catalyst.
The existing processes for the synthesis of R-isomer of Lacosamide comprise unnatural amino acid D-serine or its derivatives as starting material which is costly.
Therefore, there is need for practical and highly enantioselective synthesis of R-isomer of lacosamide using readily available, cheap starting material other than D-serine and its derivatives.
In view of the above disadvantages, the present inventors have demonstrated improved and efficient new process for the synthesis of R-lacosamide starting from commercially available (S)-benzyl glycidyl ether. Further, (S)-benzyl glycidyl ether can easily be obtained from racemic benzyl glycidyl ether using Jacobsen's HKR (hydrolytic kinetic resolution) strategy. Therefore, the objective of the present invention is to provide efficient, cost-effective and improved process for the synthesis of R-lacosimide with high enantiopurity (>98% ee) starting from readily available starting material (S)-benzyl glycidyl ether.